POS0288 A CANADIAN RETROSPECTIVE CHART REVIEW EVALUATING CONCOMITANT METHOTREXATE DE-ESCALATION PATTERNS IN RA PATIENTS TREATED WITH BIOLOGIC OR TARGETED SYNTHETIC DMARDS
Authors: L. Bessette, B. Florica, P. A. Fournier, T. Girard, L. Naik, D. Sholter, P. Baer
Journal: Annals of the Rheumatic Diseases (2022)

Background Rheumatoid arthritis (RA) guidelines recommend methotrexate (MTX) as anchor therapy in combination with biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs). However, its tolerability is challenging with a significant proportion of patients not adhering to their prescribed MTX regimen following b/tsDMARD initiation. Rates of MTX tapering and withdrawal have been reported elsewhere but Canadian data are lacking. Objectives This multi-centre, retrospective chart-based cohort study assessed the frequency of MTX withdrawal or tapering following initiation of a b/tsDMARD in Canadian adults with RA. Methods Patients were eligible if they received MTX for ≥3 months before initiation of a b/tsDMARD that was then prescribed continuously for ≥18 months and was initiated in combination with MTX. Patients taking oral prednisone or equivalent at a dose &gt;10 mg per day, and those whose b/tsDMARD was prescribed prior to 2014, were excluded. Results Data from 889 patients were included in the analysis. Mean age was 50.6 years and 72.6% were female. Mean time since diagnosis was approximately 8 years. Of the 46.1% of patients with a documented assessment of disease status at baseline, 62.7% of patients had high disease activity. Baseline mean (SD) MTX dose was 18.9 (6.63) mg/week, administered orally (57.4%), subcutaneously (41.3%), or intramuscularly (1.2%). Overall, 270 (30.4%) patients either tapered (123, 13.8%) or discontinued (147, 16.5%) their MTX within 2 years of initiating the b/tsDMARD. Methotrexate dose was unchanged for 582 (65.5%) subjects and increased for 37 (4.2%) subjects. The prescribed b/tsDMARD was most often a tumor necrosis factor inhibitor (TNFi,52.1%), followed by a Janus kinase inhibitor (JAKi, 18.3%), other modes of action (OMA) which included abatacept and rituximab (17.7%) and interleukin-6 inhibitor (IL-6i, 11.9%). The b/tsDMARD type with the highest frequency of MTX Taper or Discontinued was IL-6i (37 patients, 34.9%) followed by TNFi (144 patients, 31.1%), JAKi (47 patients, 28.8%) and OMA (44 patients, 28.0%). In the MTX Discontinued group, the most common reasons for MTX discontinuation were patient decision (27.2%) and adverse events (24.5%). In the MTX Tapered group, the most common reasons for MTX dose change were planned tapering (36.6%) and adverse events (29.3%). In the MTX Increased group, insufficient clinical response (73.0%) was the most common reason provided for MTX dose change. Baseline factors associated with MTX dose discontinuation and tapering by multiple logistic regression were a shorter time since diagnosis (Odds ratio [OR]: 0.981; 95% confidence interval [CI]: 0.964 – 0.999. P=0.0401), use of non-DMARD medications excluding steroids (OR: 0.683; 95%CI: 0.503 – 0.929. P=0.0150) and a greater number of comorbidities (OR: 1.054; 95%CI: 1.001 – 1.110. P=0.0444). The mean (SD) weekly MTX dose at the end of the data extraction period was 14.13 (4.81) mg for the MTX Tapered group, with 109 (88.6%) subjects taking a weekly MTX dose ≥10 mg. In the MTX Increased group the mean (SD) weekly MTX dose was 22.3 (3.74) mg. Interpretation of the effect of MTX dose on disease activity, fatigue, pain and functional status is challenging due to missing data, but most patients in all 4 groups transitioned to low disease activity or remission during the study period. Conclusion Methotrexate withdrawal or tapering occurred in 30.4% of Canadians with RA within two years following b/tsDMARD initiation. There was no evidence of worsening disease activity in these patients. These proportion of Canadian RA patients who reduce or discontinue MTX after the initiation of a ts/bDMARD are generally consistent with those reported in other regions of the world. Acknowledgements AbbVie Corp. funded the research for this study and provided writing support for this abstract. AbbVie participated in the study design; study research; collection, analysis, and interpretation of data; and writing, reviewing, and approving this abstract for submission. All authors had access to the data; participated in the development, review, and approval of the abstract; and agreed to submit this abstract to EULAR 2022. AbbVie and the authors thank all study investigators for their contributions and the patients who participated in this study. Medical writing support was provided by John Howell PhD of McDougall Scientific and funded by AbbVie, Inc. Disclosure of Interests Louis Bessette Speakers bureau: Amgen, BMS, Janssen, UCB, AbbVie, Pfizer, Merck, Lilly, Novartis, Sanofi, Sandoz, Gilead, Fresenius Kabi, Consultant of: Amgen, BMS, Janssen, UCB, AbbVie, Pfizer, Merck, Lilly, Novartis, Sanofi, Sandoz, Gilead, Fresenius Kabi, Grant/research support from: Amgen, BMS, Janssen, UCB, AbbVie, Pfizer, Merck, Lilly, Novartis, Sanofi, Sandoz, Gilead, Fresenius Kabi, Brandusa Florica Speakers bureau: AbbVie, Amgen, Lilly, Pfizer, Janssen, Novartis, Merck, Consultant of: AbbVie, Amgen, Lilly, Pfizer, Janssen, Novartis, Merck, Grant/research support from: AbbVie, Amgen, Lilly, Pfizer, Janssen, Novartis, Merck, Pierre-André Fournier Shareholder of: AbbVie, Employee of: AbbVie, Tanya Girard Shareholder of: AbbVie, Employee of: AbbVie, Latha Naik Speakers bureau: AbbVie, Consultant of: AbbVie, Grant/research support from: AbbVie, Dalton Sholter Speakers bureau: AbbVie, Amgen, BMS, Celgene, Gilead, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, Sandoz, UCB, Consultant of: AbbVie, Amgen, BMS, Celgene, Gilead, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, Sandoz, UCB, Grant/research support from: AbbVie, Amgen, BMS, Celgene, Gilead, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, Sandoz, UCB, Philip Baer Speakers bureau: Abbvie, Amgen, Lilly, Pfizer, Janssen, Teva, Fresenius Kabi, Viatris, Opticann, Novartis, Organon, Gilead, Celltrion, Astra Zeneca, GSK, Consultant of: Abbvie, Amgen, Lilly, Pfizer, Janssen, Teva, Fresenius Kabi, Viatris, Opticann, Novartis, Organon, Gilead, Celltrion, Astra Zeneca, GSK, Grant/research support from: Abbvie, Amgen, Lilly, Pfizer, Janssen, Teva, Fresenius Kabi, Viatris, Opticann, Novartis, Organon, Gilead, Celltrion, Astra Zeneca, GSK